Optically active 2-hydroxycarboxylic acids represented by the general formula (1):
(wherein R1 represents a substituted or unsubstituted alkyl group containing 1 to 12 carbon atoms, a substituted or unsubstituted aryl group containing 6 to 14 carbon atoms or a substituted or unsubstituted aralkyl group containing 7 to 15 carbon atoms) are important intermediates in the production of pharmaceuticals (for example, Biosci. Biotech. Biochem., 60 (8), 1279–1283, 1996) and, for the production thereof, the following methods are known, among others:    (i) L-Phenylalanine hydrochloride is prepared by treating L-phenylalanine with concentrated hydrochloric acid in chloroform and, then, (2S)-2-hydroxy-3-phenylpropionic acid is synthesized by treating an aqueous solution (proton concentration 1.4 mol/kg) containing L-phenylalanine and 4 equivalents, relative to L-phenylalanine, of a protonic acid (hydrochloric acid and sulfuric acid) with an aqueous solution containing 2 moles of sodium nitrite per mole of L-phenylalanine at 0° C. for 3 hours. After the reaction, the (2S)-2-hydroxy-3-phenylpropionic acid is recovered as crystals by ether extraction, dehydration, ether extract concentration and treatment of the residue with benzene (isolation yield 40%) (J. Amer. Chem. Soc., 86, 5326–5330, 1964);    (ii) (2S)-2-Hydroxy-3-phenylpropionic acid is synthesized by adding 4 moles, per mole of L-phenylalanine, of solid sodium nitrite to an aqueous solution (proton concentration 2.1 mol/kg) containing L-phenylalanine and 4 equivalents, relative to L-phenylalanine, of a protonic acid (sulfuric acid) at 0° C. over 5 hours, gradually warming the mixture to room temperature and stirring the same overnight. After the reaction, the (2S)-2-hydroxy-3-phenylpropionic acid is recovered as crystals by two or more times of extraction with ethyl acetate, washing of the extract with a saturated aqueous solution of sodium chloride, dehydration of the same over magnesium sulfate, concentration of the ethyl acetate solution and crystallization by addition of hexane (isolation yield 50%) (J. Heterocyclic Chem., 29, 431–438, 1992).
However, check experiments made by the present inventors concerning the above method (i) revealed that the method has such problems as the use of chloroform and benzene, which are highly toxic organic solvents, and the very low reaction yield (42%).
Checking of the above method (ii) by experiment revealed such problems as procedure complicatedness and increased capacity requirement, as resulting from the use of solid sodium nitrite and of large amounts of organic solvents and inorganic salts. It was also revealed that the reaction yield itself is low, namely 65%. In Biosci. Biotech. Biochem., 60 (8), 1279–1283, 1996, it is noted to the effect that the above method (ii) allows the formation, as a byproduct, of a large amount of a related substance (cinnamic acid) and accordingly gives a low yield, hence it is very difficult to employ that method on a commercial scale.
Further, it was revealed that the above methods (i) and (ii) still have another problem in that the optical purity is reduced by the formation of a considerable amount of the optical isomer (2R)-2-hydroxy-3-phenylpropionic acid as a byproduct as a result of racemization.
With such a background, alternative methods of producing optically active 2-hydroxy-3-phenylpropionic acid have been made, for example the method comprising asymmetric reduction of racemic 2-hydroxy-3-phenylpropionitrile using a microorganism (e.g. Biosci. Biotech, Biochem., 60 (8), 1279–1283, 1996 and JP-A 6-237789). These method are, however, not entirely favorable since the cyano compound to be used is highly toxic, the productivity is low and, further, no satisfactory optical purity can be obtained.
As for the production of optically active carboxylic acids substituted by a chlorine atom in the 2-position, which are represented by the general formula (2):
(wherein R1 is as defined above) the following are known in the art:    (i) The method comprising using an amino acid as a starting material and chlorinating the same using sodium nitrite while retaining the configuration thereof (Liebigs Ann., 1907, 357, 1); and    (ii) The method comprising chlorinating a 2-hydroxycarboxylic acid ester with configurational inversion (JP-A 61-57534).
However, the method (i) indeed gives a 2-chlorocarboxylic acid whose configuration at 2-position is (S) when a naturally occurring L-amino acid is used as the starting material but, for producing a 2-chlorocarboxylic acid whose configuration at 2-position is (R), it requires the use of a non-natural D amino acid, which is expensive, as the starting material, hence it has its limit as a method of producing (R)-2-chlorocarboxylic acids.
As for the method (ii), it is necessary to derivatize a 2-hydroxycarboxylic acid into a 2-hydroxycarboxylic acid ester, chlorinate the same with configurational inversion and then derivatize the chlorination product into a 2-chlorocarboxylic acid by hydrolysis. Thus, a number of steps have to be required and the method is not efficient.
Further, optically active 2-acetylthiocarboxylic acids represented by the general formula (3):
(wherein R1 is as defined above) are important intermediates in the production of pharmaceuticals (e.g. as intermediates of antihypertensive agents; cf. JP-A 8-337527). For the production thereof, the following are known in the art:    (i) The method comprising thioacetylating a non-natural D-amino acid via configuration-retaining bromination (JP-A 8-337527 etc.);    (ii) The method comprising optical resolution of a racemic 2-acetylthiocarboxylic acid (JP-A 6-56790);    (iii) The method comprising hydrolyzing a thiazoline compound by means of a microorganism (JP-A 11-192097); and    (iv) The method comprising stereoseletively reducing a di-substituted acrylic acid derivative by means of a microorganism (JP-A 11-196889).
However, for producing an (S) form, the method (i) requires the use of an expensive non-natural D-amino acid as the starting material, hence it has its limit as a method of producing (S) forms.
The method (ii) lies in optical resolution of racemic 2-acetylthiocarboxylic acids, hence is not so efficient but has a problem from the industrial utilization viewpoint.
The method (iii) requires a separate procedure for increasing the optical purity since the 2-thiocarboxylic acid derivative obtained by hydrolysis of the thiohydantoin derivative has an optical purity as low as 82% ee. Thus it has a problem from the industrial utilization viewpoint.
The method (iv) is low in yield of asymmetric reduction of mercaptoacrylic acid derivative, namely 60 to 70% and, further, the 2-thiocarboxylic acid derivative obtained has an optical purity as low as 90% ee. Thus it has problems from the industrial utilization viewpoint.